Worley Brittany V, Schilly Kelci M, Schoenfisch Mark H
Department of Chemistry, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, United States.
Mol Pharm. 2015 May 4;12(5):1573-83. doi: 10.1021/acs.molpharmaceut.5b00006. Epub 2015 Apr 15.
Herein, we describe the synthesis of nitric oxide (NO)-releasing alkyl chain modified poly(amidoamine) (PAMAM) dendrimers of various sizes (i.e., generations). Generation 1 (G1) through generation 4 (G4) dendrimers were modified with either short (i.e., butyl) or medium (i.e., hexyl) alkyl chains via a ring-opening reaction. The resulting secondary amines were subsequently modified with N-diazeniumdiolate NO donors to establish NO payloads of ∼1.0 μmol/mg. The bactericidal efficacy of these dendrimers was evaluated against Gram-negative and Gram-positive biofilms, including antibiotic-resistant strains. The anti-biofilm action of the dendrimer biocides was found to be dependent on dendrimer generation, bacterial Gram class, and alkyl chain length, with the most effective biofilm eradication occurring when antibacterial agents were capable of efficient biofilm infiltration. The addition of NO release markedly enhanced anti-biofilm activity of dendrimers incapable of effective biofilm penetration.
在此，我们描述了不同尺寸（即代数）的释放一氧化氮（NO）的烷基链修饰聚（酰胺胺）（PAMAM）树枝状大分子的合成。通过开环反应，用短链（即丁基）或中链（即己基）烷基链对第1代（G1）至第4代（G4）树枝状大分子进行修饰。随后，用N - 二醇二氮烯鎓NO供体对所得仲胺进行修饰，以建立约1.0 μmol/mg的NO负载量。评估了这些树枝状大分子对革兰氏阴性和革兰氏阳性生物膜（包括耐药菌株）的杀菌效果。发现树枝状大分子杀菌剂的抗生物膜作用取决于树枝状大分子的代数、细菌革兰氏类别和烷基链长度，当抗菌剂能够有效渗透生物膜时，生物膜根除效果最佳。NO释放的加入显著增强了无法有效穿透生物膜的树枝状大分子的抗生物膜活性。
